The fountain of youth of mitochondrial research

[RapAdmin]

Research is targeting mitochondrial dysfunction to tackle aging and much more, but hype is an increasing concern

Mitochondria in our cells take components from the food we eat and turn them into energy. This essential role in energy metabolism is fundamental to the way cells work and the existence of complex life. Mitochondria are not only essential cellular energy factories; they also have critical functions that extend to cell signaling and are essential for everything from muscle and neuronal function to responses to viral infections. However, as they play such a pivotal role in health, defects in mitochondrial functions can also be responsible for a wide range of diseases. One group includes primary mitochondrial diseases, a range of genetic disorders that can result in heart failure, blindness, muscle weakness, and death. Another is secondary mitochondrial diseases: neurodegenerative disorders, cancer, diabetes, and obesity that have a component of mitochondrial dysfunction. Critically, defects in mitochondria, as well as primary and secondary mitochondrial diseases, have also been linked with aging‐associated processes.

https://www.embopress.org/doi/full/10.15252/embr.202358118

[John_Hemming]

What i find interesting is that in TCM Yang Qi herbs all seem to be AMPK activators. Perhaps there is something in this?

[desertshores]

Once again methylene blue comes to the rescue. I really don’t understand why methylene blue failed the ITP other than mice are not men.

“Methylene blue is a redox drug that has been shown to help the electron transport mechanism in mitochondria by donating electrons directly to the electron transport chain. This allows methylene blue to increase mitochondrial respiration and ATP production”
Mechanism

Methylene blue can reroute electrons in the mitochondrial electron transfer chain directly from NADH to cytochrome c, bypassing complexes I and III.

This increases the activity of complex IV and effectively promotes mitochondrial activity while mitigating oxidative stress
.
The unique auto-oxidizing redox chemical property of methylene blue allows it to stimulate mitochondrial respiration by donating electrons.

Methylene blue accepts electrons from reducing equivalents in mitochondria and transfers them to other components of the respiratory chain or molecular oxygen."

The evidence suggests that methylene blue can help the electron transport mechanism and improve mitochondrial respiration by donating electrons directly to the electron transport chain. This allows bypassing of complexes I and III, increasing ATP production and decreasing oxidative stress.

Coenzyme Q10 and vitamin K2 are two other supplements that can help donate electrons directly to the electron transport chain and improve mitochondrial respiration. Coenzyme Q10 acts as an electron carrier in the chain, accepting electrons from complexes I and II and transferring them to complex III. Vitamin K2, in its reduced form, can also donate electrons to ubiquinone in the chain. Additionally, some evidence suggests creatine supplements may help improve mitochondrial respiration by donating phosphate to ADP to regenerate ATP.

I have already posted links to the relevant papers, so I won’t post the links again, but here are the titles:

From Mitochondrial Function to Neuroprotection-an Emerging Role for Methylene Blue. (Molecular neurobiology, 2018)

Methylene blue improves mitochondrial respiration and decreases oxidative stress in a substrate-dependent manner in diabetic rat hearts. (Canadian journal of physiology and pharmacology, 2017)

The photodynamic and direct actions of methylene blue on mitochondrial energy metabolism: A balance of the useful and harmful effects of this photosensitizer. (Free radical biology & medicine, 2020)

Molecular Mechanisms of the Neuroprotective Effect of Methylene Blue. (Biochemistry. Biokhimiia, 2022)

Alternative mitochondrial electron transfer for the treatment of neurodegenerative diseases and cancers: Methylene blue connects the dots. (Progress in neurobiology, 2017)

Protective role of methylene blue in Alzheimer’s disease via mitochondria and cytochrome c oxidase. (Journal of Alzheimer’s disease : JAD, 2010)

Bypassing the compromised mitochondrial electron transport with methylene blue alleviates efavirenz/isoniazid-induced oxidant stress and mitochondria-mediated cell death in mouse hepatocytes. (Redox biology, 2014)

Therapeutic benefits of methylene blue on cognitive impairment during chronic cerebral hypoperfusion. (Journal of Alzheimer’s disease : JAD, 2014)

Neurometabolic mechanisms for memory enhancement and neuroprotection of methylene blue. (Progress in neurobiology, 2012)

Alternative mitochondrial electron transfer as a novel strategy for neuroprotection. (The Journal of biological chemistry, 2011)

[L_H]

Could it be that mice studies are too narrowly focussed on cancer avoidance? (because that’s what lab mice tend to die from). Something I’d love to learn more about is the role of mitochondrial dysfunction and cancer.
Whilst I’m totally convinced mitochondrial improvement in humans will lead to greater longevity/healthspan. I’m not convinced that it does with lab Mice.

@desertshores do you regard methylene blue, k2, CoQ10 as largely interchangeable when it comes to their mitochondrial impact. Or do you favour some over others (or favour cycling between them)?

[John_Hemming]

Professor Thomas Seyfried argues a metabolic theory of cancer in that when the mitochondria get sufficiently dysfunctional fermentation takes over and you get cancer.

He has done quite a few Youtube interviews and I posted some of his papers on another thread, but here is a video.

Shocking Truth About Cancer: Fix Your Diet & Lifestyle To Starve It For Longevity | Thomas Seyfried

[RufusDawes]

giving this topic a bump for a worthy topic

I finally tried MB after wanting to for a few years. The blue mouth was holding me back Lol
Really impressed, gives a great mental focus boost, along with increased energy taken in the morning… can feel the effects taper off late in the afternoon.

Easy to administer: 10 drops in a shot glass of water, slam it down like a shot of tequila right to the back of your throat, no blue mouth or tongue. You can take this dose twice per day if you wish, I only take it once for now.

Give it a try for a $20 bottle on Amazon, you might be impressed like I was. I’m adding it to my weekly schedule, taking it on days when I don’t take weekly Rap or twice a week Enclomiphene Citrate (part of my Test stack).

[Agetron]

Directions with the MB product says let it stand in sunlight for 3 hours to activate or charge the electrons. Thoughts?

[Curious]

At approximately the 26-minute mark, Prof Dodick lists MB as one of the drugs that target both aging and brain health. I have started with micro-dosing MB in the morning. I do not mix the MB with water. But if adding ascorbic acid and diluting MB with water will reduce the staining on the lips and tongue, that might be an option. As for now. I fill an empty capsule with MB and swallow it that way…

David W. Dodick at ARDD2024: Brain health and longevity

[Agetron]

Nice… MB does great on longevity. See chart.
Would have thought rapamycin would have done better… it’s good for limited human trials.

Just got mine (MB), as soon as I set up with distilled water, sunlight and absorbic acid… will give it a try.

Thinking I will make a big batch…put it in plastic water bottles… use as needed from the refrigerator.

Pink highlights are drugs in trials with placebos for dementia.

[Curious]

When it comes to dosing, it is a tricky supplement. Low dose might give one effect, and high dose might produce another effect. Some in this forum have much more experience with MB than me. @约瑟夫_拉维尔

But that aside, I found this German Doctor who takes Mb himself and prescribes to his patients. He uses low-dose therapy.

The Science And Benefits Of Methylene Blue

And this is what ascorbic acid does to MB. Same amount of MB in both glasses. In the right one, I added 500 mg vitamin C.

I tried to rub the light blue mix of Vit C and MB on my hand and It did not color my hand at all. Amazing.

usually the stains are terrible to get rid off.

[Joseph_Lavelle]

@Curious be sure to look this thread on MB. Lots of good info.

Is methylene blue useful?

Here are my notes from memory of my talk with Dr Scott Sherr, Internal Medicine MD about methylene blue. Podcast episode to be published in a few weeks. MB is a mitochondria booster. It helps mitochondria all over body to make more energy and reduce ROS. You will feel it where you need it: brain fog, muscle fatigue resistance, thyroid caused low metabolism. Avoid vit c with MB. Dr scott Sherr thinks it lowers the effectiveness of the MB. My thought: Maybe use as little bit c as possible if cannot avoid. Titrate dose upward until you feel it. Watch pee color…until you get a bright blue color you haven’t maxed the dose…keep going, or until you feel it. Don’t take forever if you can fix the underlying reason for the mitochondria disfunction. MB is a good bridge until you can solve the underlying root cause. Low doses are best especially for long term usage. 50mg+ is best for infection, recovery from injury etc. 8-16mg works for most people and is low enough for long term use. Can u…

[Agetron]

I can’t believe all the blue mouths. The instructions with my brand are very clear… add absorbic acid… aka vitamin C. It does not harm the benefits of MB and you get a dose of vitamin C. The direction says vitamin C improves MB absorption. Be sure to let the water and MB sit in the sunlight for 3 hours… it charges the electrons… to active.

I was waiting for a nice sunny day… today was perfect made a week’s worth.

Made one at a time… unscrewed lid . Put an eye dropper full of MB in… added 1000 mg of vitamin C.

You can see each water bottle changing from dark blue to almost clear.

After 10 minutes all were clear.

Will refrigerator the lot and use as needed.

[Joseph_Lavelle]

@Agetron

it charges the electrons

Report back on your experience.

I doubt charging the solution matters a lot as the MB is an electron recycler aiding the ETC. In any case, I find MB helps my body in several important ways when I need it. And thanks for the reminder…I’m going to get 15 drops right now (I just use the eye dropper to put at the back of my throat).

[Curious]

I either put a few drops in a capsule or use the vitamin C… I micro dose, my max doce is now 10 drops. So no blue mouth here.

[RapAdmin]

don’t drink too much

Paul Karason

[DeStrider]

He died in 2013 from pneumonia following a heart attack and stroke.

Maybe he should have tried Ezetemibe, a statin and doxycycline instead?

[Agetron]

Hahaha… took my MB for the first time with my night’s supplements… D3…K2… Magnesium…Calcium … Melatonin… Lecithin… etc.

Slept good… got up… took my morning pee… was surprised how clear my pee was…

And… then… it was more and more light blue… was a long pee…hahaha. The toilet bowl looked like it had one of those bluing cleaners… WOW!. It came out… more light blue… than it went in … like it reversed somehow.

Ummm… is this typical? I mean Joseph shoots it full strength at the back of his throat. Surely… his pee has to show the same bluing.

Going to go with once at night… not doing 2. Don’t want to look like a Smuf. Hahaha

[John_Hemming]

Its a ph Balance thingy.

[Joseph_Lavelle]

@Agetron My experience is the same. I started using MB with vitamin C (drank a clear fluid) but my pee was still blue. But the use of Vit c or not does not affect the blueness of the pee. What does affect it is dose and “need for support”. This last bit is from Dr Scott Sherr (during my interview). He said if your pee is clear or faintly blue, then increase the dose. He was speaking to the claim from some people that “don’t feel anything”….he said increase the dose, and an indication of too low a dose is no or low blue color in pee.

In addition I find it takes a while (4-6 hours +-) for the MB to show up in my pee. But I feel it within minutes.

Dr Sherr says it improves mito efficiency everywhere but you feel it where you need it (brain fog, infection clearance, etc)

[dicarlo2]

Increasing the dose eventually results in MAOI activity. Perhaps people start to feel better when they initially feel nothing because they have higher levels of neurotransmitters.

This occurs for me at ~60mg of methylene blue. Anything less and I feel nothing, which probably indicates that my mitochondria are fine and/or how MB helps the mitochondria is not effective for me.